Retroviral vectors have been developed which produce a secreted form of the receptor for the HIV virus, the human CD4 T-cell antigen. Amphotropic retroviral packaging cell lines were used to produce viral-vector particles which were then used to transduce a wide variety of cell types (including primary human cells) . The production of the secreted CD4 molecule (sCD4) by transduced cells was demonstrated by immunoprecipitation and radioimmunoassay. Co-culture protection experiments were initiated in which human T-cell lines were grown in the presence of transduced cells secreting low levels of sCD4. The co-culture was then challenged with HIV-1 and productive infection assayed by syncytia formation and p24 production. Significant protection from HIV infection was observed in co-cultures producing sCD4. sCD4 retroviral vectors could potentially be used to engineer the cells of an HIV infected individual, and data indicate this strategy may be a potential gene therapy approach for the treatment of AIDS.